The goal of this NCRR SIG grant proposal is to acquire a state-of-the-art laser-scanning confocal microscope to support research of 14 NIH-funded Investigators (PIs) at the New England Primate Research Center (NEPRC), a major research facility at Harvard Medical School (HMS). NEPRC is a NCRR supported national primate center that pursues a mission that integrates research, training, and services in biology and medicine, focusing on human health and primate biology. The existing multi-user confocal system, a Leica TCS SP1 purchased in 1998, has served as a workhorse for us over 10 years and provided outstanding service to the broad research community at NEPRC. While it was state-of-the-art in the 1990's, this heavily- used, aging system no longer meets our needs in temporal and spatial resolution, photosensitivity, imaging quality, and versatility. This system is incapable of supporting many novel and powerful applications available in today's molecular/cellular/system imaging applications and is not upgradeable. We present research projects from 14 investigators (11 Major Users and 3 Minor Users) at NEPRC and affiliated institutions. These projects represent a broad array of research interests ranging from molecular and cellular neurobiology to neurological and psychiatric disorders, from microbiology to AIDS pathogenesis, and from molecular virology to cancer. Each major user has in common a strong history of NIH funding (they receive in excess of $10M in direct NIH funds per year from 10 categorical institutes) and a need for advanced imaging technology. We propose to purchase a Leica TCS SP5 405UV Spectral Confocal Microscope system with an inverted microscope, 8 laser lines with AOBS, a UV 405 laser, prism spectrophotometer detectors and easy-to-use advanced software with FRAP and FRET controls, all of which are essential to the projects proposed by the major users. Compared to other premiere systems on the market, the Leica TCS SP5 offers the best overall package in quality, options, service, and price. It also permits enormous power and flexibility and accommodates many novel applications that fit into the needs of diverse research interests at NEPRC. The system will be housed in the NEPRC imaging core facility, maintained by a highly experienced core staff, and supported by a NCRR base grant. The new confocal system would be essential to the NIH-sponsored research of the Major and Minor users at NEPRC, and greatly facilitate the overall mission of the NEPRC as a national center for research, service, and training. The research to be performed with this system will have direct impact on understanding the molecular and cellular basis of a range of neurological, psychiatric, and infectious diseases.